Transitional cell carcinoma of the bladder is a highly recurrent and the most common form of bladder cancer in the United States. It is very expensive to monitor and treat this form of bladder cancer. The urothelium is highly susceptible to carcinogen-induced cancer such as carcinogens from cigarette smoke. Our goal is to develop naturally occurring chemopreventive agents to prevent bladder cancer. Our preliminary data suggest that capsaicin inhibits the growth of bladder cancer cells in culture. We have proposed that capsaicin can be an effective primary chemoprevention agent by virtue of its ability to modulate carcinogen metabolism and detoxification enzymes. We have also proposed that capsaicin can inhibit tumor growth in a preclinical model of bladder cancer by selectively inducing apoptosis in cancer cells that are under oxidative stress. Completion of the proposed experiments will provide evidence regarding the potential of capsaicin as a chemopreventive agent for bladder cancer. This data will allow submission of subsequent proposals to test capsaicin as an agent to prevent recurrent transitional bladder cancer as well muscle invasive bladder cancer. The long term goal is clinical translation of capsaicin to decrease morbidity and economic burden related to bladder cancer. Transitional cell carcinoma (TCC) is by far the most frequently diagnosed bladder cancer in the US. It is one of the most expensive cancers to monitor and treat;and therefore a great economic burden. In this pilot proposal we will test the premise that a naturally occurring compound called capsaicin found in chili peppers can prevent TCC development by changing the cell survival milieu of bladder cancer cells.